Identification of γ-butyrolactone signalling molecules in diverse actinomycetes using resin-assisted isolation and chemoenzymatic synthesis.

IF 4.2 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Yuta Kudo, Keiichi Konoki, Mari Yotsu-Yamashita
{"title":"Identification of γ-butyrolactone signalling molecules in diverse actinomycetes using resin-assisted isolation and chemoenzymatic synthesis.","authors":"Yuta Kudo, Keiichi Konoki, Mari Yotsu-Yamashita","doi":"10.1039/d5cb00007f","DOIUrl":null,"url":null,"abstract":"<p><p>Actinomycetes are prolific producers of secondary metabolites with diverse bioactivities. Secondary metabolism in actinomycetes is regulated by signalling molecules, often termed \"bacterial hormones.\" In <i>Streptomyces griseus</i>, the γ-butyrolactone (GBL) A-factor (1) plays a key role in regulating secondary metabolism, including streptomycin production. The widespread presence of <i>afsA</i>, the gene encoding A-factor synthase, suggests that GBLs are a major class of signalling molecules in actinomycetes. However, their identification is hindered by the requirement for large-scale cultures. This study presents two methodologies for identifying natural GBLs. First, a resin-assisted culture method combined with MS-guided screening enabled the isolation and structural determination of GBLs (2-5) from smaller-scale cultures. Second, a chemoenzymatic synthesis method involving one-pot three enzymatic reactions was developed, allowing the production of GBL standards (10a-10l). Using these standards, HR-LCMS analysis of 31 strains across 10 actinomycetes genera identified GBLs in nearly half of the tested strains, including genera where GBLs were detected for the first time. Chiral HPLC analysis further revealed the presence of the (3<i>S</i>)-isomer of GBL (11), an enantiomer of known GBLs. This study uncovers the widespread distribution and structural diversity of GBLs among actinomycetes, providing insights into their regulatory roles and potential for activating secondary metabolism, which may facilitate the discovery of new natural products.</p>","PeriodicalId":40691,"journal":{"name":"RSC Chemical Biology","volume":" ","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11877004/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"RSC Chemical Biology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1039/d5cb00007f","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Actinomycetes are prolific producers of secondary metabolites with diverse bioactivities. Secondary metabolism in actinomycetes is regulated by signalling molecules, often termed "bacterial hormones." In Streptomyces griseus, the γ-butyrolactone (GBL) A-factor (1) plays a key role in regulating secondary metabolism, including streptomycin production. The widespread presence of afsA, the gene encoding A-factor synthase, suggests that GBLs are a major class of signalling molecules in actinomycetes. However, their identification is hindered by the requirement for large-scale cultures. This study presents two methodologies for identifying natural GBLs. First, a resin-assisted culture method combined with MS-guided screening enabled the isolation and structural determination of GBLs (2-5) from smaller-scale cultures. Second, a chemoenzymatic synthesis method involving one-pot three enzymatic reactions was developed, allowing the production of GBL standards (10a-10l). Using these standards, HR-LCMS analysis of 31 strains across 10 actinomycetes genera identified GBLs in nearly half of the tested strains, including genera where GBLs were detected for the first time. Chiral HPLC analysis further revealed the presence of the (3S)-isomer of GBL (11), an enantiomer of known GBLs. This study uncovers the widespread distribution and structural diversity of GBLs among actinomycetes, providing insights into their regulatory roles and potential for activating secondary metabolism, which may facilitate the discovery of new natural products.

求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.10
自引率
0.00%
发文量
128
审稿时长
10 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信